The separate effects of aging and of obesity in estrogen physiology in men and women are not yet clearly delineated. In addition, from previous work, several discrepancies or anomalies are noted, particulary between the results of radioactive studies and endogenous studies in plasma and urine. We propose a series of experiments which will use several unique capabilities of our laboratory to establish the separate and interacting consequences of aging and of obesity on certain aspects of estrogen physiology. In particular, we shall compare the results of specially-designed radioactive and endogenous experiments to explain the previously-noted discrepancies. This should result in substantially increased understanding in these areas. In addition, we shall add new knowledge directly, by establishing the separate effects of aging and obesity on the levels of estrogen conjugates, in plasma and urine. We shall determine the separate effects of aging and obesity on the renal clearance of estrogens and estrogen conjugates. Finally, we shall determine the effects of aging and obesity on the plasma protein binding of estrogen and estrogen conjugates, with particular reference to albumin binding. These studies should not only add substantially to our knowledge of estrogen physiology in general, and further delineate the effecst of aging and obesity, but also may allow the identification of certain predictive factors (predisposing or protective) for diseases such as breast cancer and endometrial cancer, which are both related to age and obesity.